The purpose of this proposal is to continue and extend the previous work supported by grant AI-23004, to delineate both the antigens and mechanisms involved in protective immunity for leishmaniasis. In addition, the proposal is to investigate biochemical differences responsible for the survival of the parasite in each of the life cycle stages (promastigote- amastigote). The specific aims are: 1. Identification and evaluation (in vivo) of antigens protective against an infection with Leishmania sp.. 2. Elucidation of the effector mechanisms involved in a protective immune response against leishmaniasis. 3. Development of methods/strains for the axenic culture of Leishmania amastigotes. 4. Molecular biological, biochemical, and biological characterization of stage-specific antigens (promastigote and amastigote) of Leishmania. 5. Studies of the M-2 Gene Family. 6. Molecular cloning of stage-specific and protective antigens. 7. Development of a reliable specific serological diagnostic assay for visceral leishmaniasis. The aims of this proposal are essentially those of the original proposal; however, the methodology and approaches being taken have been expended based on the progress that has occurred during the past two years.